subject:(lysophosphatidic acid)

University of Utah

1. Serban, Monica A. Hyaluronian-based synthetic extracellular matrices: syntheses and applications;.

Degree: PhD, Medicinal Chemistry;, 2007, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/362/rec/626

► In mammalian tissues, cells are surrounded by the extracellular matrix (ECM) – a complex network of proteins, glycosaminoglycans (GAGs) and proteoglycans (PGs). The ECM regulates… (more)

▼ In mammalian tissues, cells are surrounded by the extracellular matrix (ECM) – a complex network of proteins, glycosaminoglycans (GAGs) and proteoglycans (PGs). The ECM regulates numerous crucial processes such as cell proliferation, differentiation, migrations, and a variety of signaling events. Synthetic extracellular matrices (sECMs) were developed in an attempt to mimic the properties of natural ECMs, specifically for tissue engineering applications. Several sECMs are not commercially available. We compared these materials side by side in a representative array of assays, to test their biological performances and user-friendliness. Our results indicate that the ECM composition and compliance greatly influence cell behavior. Based on these data, we underline the need for a paradigm shift from classical two-dimensional (2D) culturing to the more relevant, in vivo-like three-dimensional (3D) techniques especially for applications directly translatable to clinical applications. Haloacetate-modified hyaluronan (HA) polymers were synthesized and characterized in an effort to provide a greater variety of sECM components. A novel approach was employed that yielded “chemically-reversed,” electrophilic HA polymers that could be readily crosslinked with a variety of available nucleophiles. The new haloacetate-modified hyaluronan materials show dose-dependent mild cytotoxic effects and appear promising for adhesion prevention or medical device coating. A novel thiol-modified hyaluronan polymer (HASH) was also synthesized. These biomaterials are not crosslinkable, are well tolerated by cell and shows promising results in a rat arthritis model, by slowing down the disease progression rate. sECMs emerged to be particularly suitable for application such as drug screening. To this end, Extracel ™, a hyaluronan and gelatin-based crosslinked hydrogel was used to examine the effect of alpha-substituted lysophosphatidic acid (LPA) analogs. LPA and its synthesizing enzyme autotaxin (ATX) were associated in numerous studies with aberrant cellular behavior, mostly associated with cancer and tumorigenicity. The compounds tested show cell-line dependent and LPA receptor-specific effect in cell proliferation assays. Further studies that address modulation of cellular invasiveness and metastatic potential are needed for a complete profiling of these chemicals.

Subjects/Keywords: Fibroblast; Lysophosphatidic Acid

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APA (6^th Edition):

Serban, M. A. (2007). Hyaluronian-based synthetic extracellular matrices: syntheses and applications;. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/362/rec/626

Chicago Manual of Style (16^th Edition):

Serban, Monica A. “Hyaluronian-based synthetic extracellular matrices: syntheses and applications;.” 2007. Doctoral Dissertation, University of Utah. Accessed February 28, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/362/rec/626.

MLA Handbook (7^th Edition):

Serban, Monica A. “Hyaluronian-based synthetic extracellular matrices: syntheses and applications;.” 2007. Web. 28 Feb 2021.

Vancouver:

Serban MA. Hyaluronian-based synthetic extracellular matrices: syntheses and applications;. [Internet] [Doctoral dissertation]. University of Utah; 2007. [cited 2021 Feb 28]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/362/rec/626.

Council of Science Editors:

Serban MA. Hyaluronian-based synthetic extracellular matrices: syntheses and applications;. [Doctoral Dissertation]. University of Utah; 2007. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/362/rec/626

University of Saskatchewan

2. Algabbass, Kholud Ali. Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin.

Degree: 2016, University of Saskatchewan

URL: http://hdl.handle.net/10388/7691

► ABSTRACT Autotaxin (ATX) is a member of the nucleotide pyrophosphatase/phosphodiesterase family of ectoenzymes (NPP/ENPP). ATX is mostly present in blood, but it is also expressed… (more)

▼ ABSTRACT Autotaxin (ATX) is a member of the nucleotide pyrophosphatase/phosphodiesterase family of ectoenzymes (NPP/ENPP). ATX is mostly present in blood, but it is also expressed at high levels in the brain, kidney, lymphoid organs, ovary, lung, and intestine. ATX has lysophospholipase D activity that catalyzes the hydrolysis of lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and choline. LPA is a bioactive lipid mediator that facilitates many physiological and pathological processes including cell survival, proliferation, and migration. ATX/LPA signalling has been associated with in a number of human diseases including obesity, diabetes, rheumatoid arthritis, multiple sclerosis, neuropathic pain, Alzheimer’s disease, and cancer. Elevated ATX expression is found in various tumours and has been associated with tumour growth. Because most LPA is produced by ATX activity, an inhibitor of ATX would block subsequent LPA signalling, which is a target for anticancer drug development. Therefore, ATX has become an attractive drug target for developing new anticancer therapies. Our objective for this project is to prepare and assess a series of novel cyclic phenol phosphate analogues for their ability to function as irreversible ATX inhibitors in vitro. In order to investigate the ability of the cyclic phenol phosphate analogues to inhibit ATX, the following aims were outlined: (i) the development of synthetic methodologies for the preparation of a series of cyclic phenol phosphate analogues as potential inhibitors of ATX; (ii) an assessment of the aqueous stability of these analogues over 6 h in 50 mM TRIS buffer at 37 °C and pH 8.0 using high performance liquid chromatography (HPLC) for analysis; (iii) the determination of the ability of these compounds to inactivate ATX in vitro. In order to investigate the ability of the cyclic phenol phosphate analogues to inhibit ATX, we proposed and designed strategies to synthesize a series of acyl and alkyl ether derivatives of cyclic phenol phosphate analogues. Our initial strategy to synthesize acyl derivatives utilized the dealkylation of 1 (4-methoxy-1,3-bezenedimethanol); however, this approach was unsuccessful despite attempts to optimize reaction conditions and introduction of alcohol protecting groups. These unsuccessful reactions were likely the result of multiple competing reactions. A second strategy to synthesize alkyl ether derivatives analogues was developed, and we successfully synthesized two model analogues; A1 (unsubstituted cyclic phenol phosphate) and A2 (methoxy-substituted cyclic phenol phosphate). We accomplished this through a multi-step synthetic procedure using the salicylaldehyde and its derivatives as our starting materials. We also synthesized an alcohol starting material with a saturated fourteen-carbon ether linkage by modified literature procedures, but incorporation of the cyclic phosphate moiety was unsuccessful. We also evaluated the stability of the synthesized analogues under specific conditions. Analogues A1 and A2 were incubated… Advisors/Committee Members: Krol, Ed S., Alcorn, Jean, Yang, Jian, Sakharkar, Meena, Hill, Bryan M..

Subjects/Keywords: Autotaxin (ATX); lysophosphatidic acid (LPA); inhbitors; cancer

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APA (6^th Edition):

Algabbass, K. A. (2016). Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7691

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Algabbass, Kholud Ali. “Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin.” 2016. Thesis, University of Saskatchewan. Accessed February 28, 2021. http://hdl.handle.net/10388/7691.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Algabbass, Kholud Ali. “Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin.” 2016. Web. 28 Feb 2021.

Vancouver:

Algabbass KA. Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin. [Internet] [Thesis]. University of Saskatchewan; 2016. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10388/7691.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Algabbass KA. Activation of Cyclic Phenol Phosphate Analogues as Potential Inhibitors of Autotaxin. [Thesis]. University of Saskatchewan; 2016. Available from: http://hdl.handle.net/10388/7691

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

NSYSU

3. Huang, Jing-Long. Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats.

Degree: Master, Biological Sciences, 2015, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0027115-154427

► Lysophosphatidic acids (LPAs) belong to a class of simple phospholipids that bears signal transduction property. Upon activation by endogenous or exogenous ligands, LPA receptor (LPAR)… (more)

▼ Lysophosphatidic acids (LPAs) belong to a class of simple phospholipids that bears signal transduction property. Upon activation by endogenous or exogenous ligands, LPA receptor (LPAR) could evoke various signal transduction cascades that regulate a wide variety of cellular physiology. In the central nervous system (CNS), activation of LPAR could either trigger the signals for apoptosis or evoke the signal transductions that promote the cell survival. In our previous studies, we have morphometrically and functionally demonstrated the protective effects of VPC31143, an LPAR agonist, against the effects of permanent middle cerebral artery occlusion (pMACO) in a rat model of ischemic stroke. Nevertheless, the intracellular signal transduction mechanisms responsible for such protective effects have yet to be revealed. In this study we utilized the previously established rat model of ischemic stroke as the study foundation. Male Sprague-Dawley rats were intraperitoneally injected with 0.8 mg/kg of VPC as the therapeutic agent 30 minutes after pMCAO surgery. The motor and sensory functions of rats receiving VPC treatment (pMCAO+VPC group) and those without drug treatment (pMCAO group) were evaluated using Garcia score system at 4, 8, and 24 hrs after the pMCAO surgery. The infarct brain volume and infarct brain volume ratio of these rats were measured and calculated. The regulation of signal transduction proteins VPC-mediated LPAR activation in the ischemic rat brain hemisphere were studied with Western blot and compared to those in the ischemic hemisphere in the absence of VPC. The study results showed that LPAR activation by VPC attenuated the loss in sensory and motor functions, while concurrently reduced the infarcted brain volume ratio. The Western blot results showed that VPC treatment reduced the expression of pro-apoptotic signal proteins such as caspase 3, caspase 8, caspase 9, and phosphorylated p-38 MAPK in the ischemic hemisphere. VPC treatment also up-regulated the expression of the anti-apoptotic proteins such as PI3K, Akt, and p-42/44 MAPK in the ischemic brain, and also increased the expression of phosphorylated Bad, a mitochondrial protein critical to the integrity of this organelle. Together, the results indicated that actication of LPAR with VPC would trigger the signal pathway of PI3K as well as its downstream signal protein Akt and MAPKs, as well as other signal transduction cascades, and concurrently increase the anti-apoptotic protein expression in mitochondria. Together, these cellular mechanisms could reduce the extent of apoptosis in the ischemic brain tissues and accomplished the goal of brain protection. Advisors/Committee Members: Chiung-Yin Huang (chair), Zhi-hong, Wen (chair), Hay-Yan Jack Wang (committee member).

Subjects/Keywords: ischemic stroke; apoptosis; lysophosphatidic acid receptor; signal transduction

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APA (6^th Edition):

Huang, J. (2015). Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0027115-154427

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Huang, Jing-Long. “Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats.” 2015. Thesis, NSYSU. Accessed February 28, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0027115-154427.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Huang, Jing-Long. “Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats.” 2015. Web. 28 Feb 2021.

Vancouver:

Huang J. Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats. [Internet] [Thesis]. NSYSU; 2015. [cited 2021 Feb 28]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0027115-154427.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Huang J. Signal Transduction Mechanisms Responsible for the Protective Effects of Lysophosphatidic Acid Receptor Activation that Reduces the Ischemic Infarct Volume in Rats. [Thesis]. NSYSU; 2015. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0027115-154427

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Utah

4. Jiang, Guowei. Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;.

Degree: MS;, Medicinal Chemistry;, 2006, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1037/rec/157

► Phospholipids, including lysobisphosphatidic acid (LBPA) and lysophosphatidic acid (LPA), have been shown to mediate a variety of biological effect and are involved in various pathophysiological… (more)

Subjects/Keywords: Synthesis; Lysophosphatidic Acid receptors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jiang, G. (2006). Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;. (Masters Thesis). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1037/rec/157

Chicago Manual of Style (16^th Edition):

Jiang, Guowei. “Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;.” 2006. Masters Thesis, University of Utah. Accessed February 28, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1037/rec/157.

MLA Handbook (7^th Edition):

Jiang, Guowei. “Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;.” 2006. Web. 28 Feb 2021.

Vancouver:

Jiang G. Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;. [Internet] [Masters thesis]. University of Utah; 2006. [cited 2021 Feb 28]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1037/rec/157.

Council of Science Editors:

Jiang G. Chemical synthesis and biological evaluation of novel lysophospholipid analoguesg;. [Masters Thesis]. University of Utah; 2006. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1037/rec/157

UCLA

5. McDonald, Whitney S. The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes.

Degree: Neuroscience, 2015, UCLA

URL: http://www.escholarship.org/uc/item/8p51p37b

► Over a century of research efforts have been devoted to developing a therapy to recover loss of function after Traumatic Brain Injury (TBI). Despite these… (more)

▼ Over a century of research efforts have been devoted to developing a therapy to recover loss of function after Traumatic Brain Injury (TBI). Despite these efforts there is still no FDA approved treatment that promotes functional recovery after injury. Every year, millions of new TBI cases occur and many TBI patients have persistent loss of motor and cognitive function leaving them incapable of living independent of caregivers. There is an urgent need for a novel therapeutic that addresses the functional loss after TBI and anti-LPA therapeutic may prove effective in this regard. Progression of secondary injuries like excitotoxicity and inflammation is predictive of functional outcomes for TBI patients. Lysophosphatidic Acid (LPA) signaling is a potent mediator of the above secondary injures, despite these facts, no study has identified the role of LPA in outcomes after TBI in the adult. Fundamental issues regarding LPAs metabolic changes in the brain after injury, the effects of LPA signaling on neuroregeneration after TBI and ultimately whether intervening with Anti-LPA after TBI improves outcomes and functional recovery, require resolution in order to utilize LPA as a therapeutic target for TBI. The work herein is aimed toward gaining a more comprehensive understanding of the effects of LPA metabolism and signaling in TBI and to identify the effects of blocking LPA on injury outcomes.The first study identified the spatial and temporal profile of LPA metabolism in the injured brain and associated those changes with markers of axonal injury (Beta-APP) and cell death (Fluro-JadeB) using MALDI mass spectrometry techniques. Within 3 hour after TBI there was an enhancement of LPAs bioactive unsaturated species, as well as an increase in LPAs intra- and extra-cellular precursors at the injury epicenter in association with blood. LPA metabolism was also increased in distal regions of the brain, throughout the white matter tracts and in the cerebellum. Intracellular precursor, PA, was increased in the peri-contusional cortical grey matter and ipsilateral thalamus within 1 hour after injury and intracellular LPA increased in at 3 hours after injury in association with neuronal death markers. Pronounced expression of LPA 20:1 species was observed in the sub-cortical white matter which correlated significantly with the spatial distribution of axonal injury marker beta-APP. The data provided evidence of an increase in bioactive phospholipid metabolism throughout the brain within 3 hour of injury and associated those changes with necrosis and axonal injury. The study also identified a critical window of intervention, to potentially attenuate the increase in LPA signaling. The data suggested that LPA metabolism is involved in the early pathogenic cascades of TBI. The second study identified the effects of a one-time dose of Anti-LPA at 2 hours after injury, on secondary injury outcomes to underlie functional decline: cell death, axonal injury and inflammation. Anti-LPA intervention resulted in a reduction of white matter damage…

Subjects/Keywords: Neurosciences; Axonal Injury; Inflammation; Lysophosphatidic Acid; MALDI; Neurogenesis; Traumatic Brain Injury

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APA (6^th Edition):

McDonald, W. S. (2015). The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/8p51p37b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McDonald, Whitney S. “The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes.” 2015. Thesis, UCLA. Accessed February 28, 2021. http://www.escholarship.org/uc/item/8p51p37b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McDonald, Whitney S. “The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes.” 2015. Web. 28 Feb 2021.

Vancouver:

McDonald WS. The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes. [Internet] [Thesis]. UCLA; 2015. [cited 2021 Feb 28]. Available from: http://www.escholarship.org/uc/item/8p51p37b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McDonald WS. The role of Lysophosphatidic Acid in Traumatic Brain Injury outcomes. [Thesis]. UCLA; 2015. Available from: http://www.escholarship.org/uc/item/8p51p37b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. 이, 지연. Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation.

Degree: 2001, Ajou University

URL: http://repository.ajou.ac.kr/handle/201003/2064 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005983

Master Advisors/Committee Members: 대학원 의학과, 199824559, 이, 지연.

Subjects/Keywords: Lysophosphatidic Acid; 색소형성; igmentation

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APA (6^th Edition):

이, �. (2001). Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation. (Thesis). Ajou University. Retrieved from http://repository.ajou.ac.kr/handle/201003/2064 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005983

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

이, 지연. “Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation.” 2001. Thesis, Ajou University. Accessed February 28, 2021. http://repository.ajou.ac.kr/handle/201003/2064 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005983.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

이, 지연. “Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation.” 2001. Web. 28 Feb 2021.

Vancouver:

이 �. Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation. [Internet] [Thesis]. Ajou University; 2001. [cited 2021 Feb 28]. Available from: http://repository.ajou.ac.kr/handle/201003/2064 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005983.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

이 �. Effect of Lysophosphatidic Acid(1-acy1-glycerol 3-phosphate) on Pigmentation. [Thesis]. Ajou University; 2001. Available from: http://repository.ajou.ac.kr/handle/201003/2064 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000005983

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

7. De La Franier, Brian James. Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer.

Degree: PhD, 2017, University of Toronto

URL: http://hdl.handle.net/1807/80867

► Ovarian cancer is a disease that affects a quarter of a million new women and causes over 140,000 deaths worldwide annually. This is primarily due… (more)

▼ Ovarian cancer is a disease that affects a quarter of a million new women and causes over 140,000 deaths worldwide annually. This is primarily due to how difficult the disease is to detect, with few symptoms present in the early stages of the disease and difficult to physically feel masses. Currently detection of ovarian cancer requires time consuming and expensive imaging studies such as transvaginal ultrasound and MRI scans, which are only performed if it is already suspected that a woman has the disease. The only currently accepted blood test for ovarian cancer detects the biomarker CA-125, but this test is only sensitive to 50% of cases and as a result is rarely used for signaling the presence of the cancer. There is another biomarker for ovarian cancer called lysophosphatidic acid (LPA) which has a sensitivity and specificity of over 90% for the disease, making it promising for use in testing for ovarian cancer. There are currently no low cost or easy to perform blood tests for LPA, preventing its use as a general test that can be performed at yearly physicals. However there is a duel protein system comprised of Gelsolin and Actin which is interrupted by interactions with LPA, which can therefore be used to develop a low cost blood test for the marker. These proteins could be bound to a biosensing surface, and the release of actin as a result of LPA would generate a measurable signal. Studying the fouling behaviour of LPA and serum on transverse shear mode biosensors, also known as quartz crystal microbalances, showed that the background fouling signal was too large for a test to be developed on this class of devices. Instead a test based on colorometric sensing of dye modified actin was conceived and evaluated. This test comprised of the protein gelsolin being bound to solid phase in a way capable of holding onto the protein in serum samples. The gelsolin was also be bound to a fluorescent dye modified actin that could be measured using colorimetric absorbance or fluorescence. These proteins were successfully created, and shown to create a complex that could be broken by LPA in a concentration dependent manner. Immobilization of this protein complex was performed on silica gel, using Ni-NTA which was attached to the surface via a trichlorosilane linker functionalized with an acid chloride head group, which was first synthesized in these experiments. Several conditions in the development of the surface Ni-NTA adlayer and subsequent protein immobilization were evaluated, and it was found that such things as a large pore size in the silica gel, removal of excess toluene from the surface following adlayer addition, and adequate washing and drying of the silica were all of crucial importance to the performance of this test in serum. Development of this test showed promise in quantifying LPA at biologically relevant concentrations, however more work needs to be done to lower the limit of detection to a point below the cut-off level for ovarian cancer. Crucially this test is very cheap to produce, and requires… Advisors/Committee Members: Thompson, Michael, Chemistry.

Subjects/Keywords: Cancer; colorimetric; detection; Lysophosphatidic acid; Ovarian; screening; 0485

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

De La Franier, B. J. (2017). Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/80867

Chicago Manual of Style (16^th Edition):

De La Franier, Brian James. “Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer.” 2017. Doctoral Dissertation, University of Toronto. Accessed February 28, 2021. http://hdl.handle.net/1807/80867.

MLA Handbook (7^th Edition):

De La Franier, Brian James. “Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer.” 2017. Web. 28 Feb 2021.

Vancouver:

De La Franier BJ. Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1807/80867.

Council of Science Editors:

De La Franier BJ. Detection of Lysophosphatidic Acid in Serum; Towards a Cost Effective Test for Ovarian Cancer. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/80867

8. Mirzoyan, Koryun. The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales.

Degree: Docteur es, Physiopathologie, 2017, Université Toulouse III – Paul Sabatier

URL: http://www.theses.fr/2017TOU30073

► Les maladies rénales chroniques (MRC) et l'insuffisance rénale aiguë (IRA) sont des problèmes essentiels de santé publique en raison de l'augmentation continue de leur fréquence… (more)

▼ Les maladies rénales chroniques (MRC) et l'insuffisance rénale aiguë (IRA) sont des problèmes essentiels de santé publique en raison de l'augmentation continue de leur fréquence et du manque de solutions thérapeutiques contre ces maladies. L'acide lysophosphatidique (LPA) est un lysophospholipide bioactif qui induit un large éventail de réponses cellulaires par le biais de récepteurs membranaires spécifiques (LPA1 à LPA6) couplés aux protéines G. Dans ce travail, nous nous sommes intéressés aux effets biologiques et au métabolisme du LPA dans les MRC et l'IRA. Des travaux antérieurs de l'équipe avaient montré que le LPA contribuait, via le récepteur LPA1, au développement de la fibrose tubulointerstitio (TIF) dans un modèle de MRC chez la souris : l'obstruction urétérale. Dans la première partie de la thèse nous avons étudié l'implication du LPA dans un modèle plus avancé de MRC: la néphrectomie subtotale (SNX) chez la souris. Nos travaux ont montré que 5 mois après chirurgie les souris (SNX) développaient une albuminurie massive associée à une TIF sévère et à une hypertrophie glomérulaire. Chez ces souris la concentration en LPA mesurée par chromatographie liquide en spectrométrie de masse en tandem était augmentée dans l'urine et étroitement corrélée à l'albuminurie et à la TIF. En parallèle, nous avons observé une diminution de l'expression rénale des Lipid-Phosphate Phosphatases (LPP 1, 2 et 3) responsables de l'inactivation du LPA. Nous avons également observé que l'expression rénale des récepteurs LPA1, 2, 3 et 4 était diminuée chez les souris Snx. Nous avons conclu que les effets délétères éventuels du LPA dans le développement de la MRC chez les souris SNX était vraisemblablement lié à une augmentation de sa production rénale plutôt qu'à une sensibilité accrue du rein au LPA. Des travaux antérieurs avaient montré que l'injection de LPA protégeait contre l'apparition des lésions rénales induites par ischémie/reperfusion chez la souris. Une autre étude avait montré que le LPA permettait d'atténuer l'inflammation systémique et les dommages aux organes induits par un choc septique. Dans la deuxième partie de la thèse, nous avons étudié l'influence du LPA sur l'IRA induite par une endotoxémie au LPS (lipopolysaccharide) chez la souris. Nous avons observé que l'injection de LPA permettait d'atténuer l'élévation d'urée et de créatinine plasmatiques, ainsi que l'augmentation d'expression rénale de cytokines inflammatoires (IL-6, TNFa, MCP-1) induites par le LPS. Le LPA a également empêché la baisse d'expression rénale du facteur PGC1a ainsi que les altérations ultra-structurales des mitochondries rénales induites par le LPS. In vitro, le LPA atténue l'augmentation d'expression des cytokines pro-inflammatoires (TNFa et MCP-1) induite par le LPS dans les macrophages RAW264. Enfin, nos travaux ont montré que l'endotoxémie au LPS chez la souris entrainait une réduction de la concentration urinaire de LPA associée à une réduction des enzymes anaboliques LPA (autotaxine et acylglycérol kinase) et une élévation de… Advisors/Committee Members: Saulnier-Blache, Jean-Sébastien (thesis director).

Subjects/Keywords: Acid lysophosphatidic; Maladies rénales chroniques; Fibrose tubulointerstitio; Insuffisance rénale aiguë; Endotoxémie; Lysophosphatidic acid; Chronic kidney diseases; Tubulointerstitial fibrosis; Acute kidney injury; Endotoxemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mirzoyan, K. (2017). The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales. (Doctoral Dissertation). Université Toulouse III – Paul Sabatier. Retrieved from http://www.theses.fr/2017TOU30073

Chicago Manual of Style (16^th Edition):

Mirzoyan, Koryun. “The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales.” 2017. Doctoral Dissertation, Université Toulouse III – Paul Sabatier. Accessed February 28, 2021. http://www.theses.fr/2017TOU30073.

MLA Handbook (7^th Edition):

Mirzoyan, Koryun. “The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales.” 2017. Web. 28 Feb 2021.

Vancouver:

Mirzoyan K. The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales. [Internet] [Doctoral dissertation]. Université Toulouse III – Paul Sabatier; 2017. [cited 2021 Feb 28]. Available from: http://www.theses.fr/2017TOU30073.

Council of Science Editors:

Mirzoyan K. The role of LPA in kidney pathologies : Role du LPA dans les pathologies rénales. [Doctoral Dissertation]. Université Toulouse III – Paul Sabatier; 2017. Available from: http://www.theses.fr/2017TOU30073

Temple University

9. Goldsmith, Zachariah G. Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma.

Degree: PhD, 2009, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,34336

►

Molecular Biology and Genetics

Ovarian cancer is currently the most fatal gynecologic cancer and the fifth leading cause of fatal cancer in women overall. As… (more)

▼

Molecular Biology and Genetics

Ovarian cancer is currently the most fatal gynecologic cancer and the fifth leading cause of fatal cancer in women overall. As compared to the better-characterized malignancies, such as such as prostate, breast and colorectal cancers, there have been no major changes in methods of detection or treatment of ovarian cancers since the 1970's. As a result, the incidence and age-adjusted death rates for this disease have improved only marginally since that time. The molecular changes required for ovarian cancer pathogenesis remain poorly defined. Lysophosphatidic acid (LPA) has emerged as a biomarker present in the ascitic fluid and serum of ovarian cancer patients. Subsequent studies have identified LPA as an agonist for G protein coupled receptors (GPCRs). LPA has been well characterized as a pro-migratory factor in ovarian cancer and other cell systems. However, the role of LPA in mediating a proliferative response in ovarian cancer cells has yet to be fully characterized. In addition, the identity of the G protein pathways involved in this proliferative response remains a major unresolved question in the field. To investigate the mitogenic role of LPA in ovarian cancers, a panel of representative human ovarian cancer cells was assembled. A series of immunoblot and RT-PCR analyses was used to profile the LPA receptors and Gα-subunits expressed in these cells. In addition to verifying the migratory effect of LPA in these cells, a series of proliferation assays were used to investigate the potential role for LPA as a mitogen. The results indicate that stimulation with LPA results in a robust and statistically significant proliferative response. This response was quantified using multiple approaches. In addition, the proliferative response was observed in three independent ovarian cancer cell lines using concentrations of LPA within the range found in vivo in the ascitic fluid of ovarian cancer patients. Taken together, these data for the first time validate the role of LPA as a mitogen in ovarian cancer cells. To gain further insight into the oncogenic signaling response stimulated by LPA, activation of the mitogen activated protein kinase (MAPK) modules was determined. Using a series of immunoblot analyses and kinase assays, LPA was found to stimulate ERK as well as JNK modules. To investigate the functional roles of these pathways, a series of proliferation assays were carried out using inhibitors of ERK and JNK signaling. Consistent with the role of ERK as a crucial regulator of growth-factor induced proliferation in other cell systems, the results demonstrated a significantly attenuated growth response to LPA with ERK inhibition. Moreover, additional studies demonstrated for the first time that inhibition of JNK signaling significantly attenuates the proliferative response to LPA. In order to investigate the potential role of Gα12 in mediating the oncogenic response to LPA, the activation status of Gα12 was monitored in ovarian cancer cells stimulated with LPA. These studies…

Advisors/Committee Members: Dhanasekaran, Danny, Shore, Scott K., Liebermann, Dan A., Athwal, Raghbir S., Kelsen, Steven G..

Subjects/Keywords: Biology, Molecular; Health Sciences, Oncology; ERK; G alpha 12; JNK; LPA; lysophosphatidic acid; ovarian cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Goldsmith, Z. G. (2009). Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,34336

Chicago Manual of Style (16^th Edition):

Goldsmith, Zachariah G. “Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma.” 2009. Doctoral Dissertation, Temple University. Accessed February 28, 2021. http://digital.library.temple.edu/u?/p245801coll10,34336.

MLA Handbook (7^th Edition):

Goldsmith, Zachariah G. “Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma.” 2009. Web. 28 Feb 2021.

Vancouver:

Goldsmith ZG. Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma. [Internet] [Doctoral dissertation]. Temple University; 2009. [cited 2021 Feb 28]. Available from: http://digital.library.temple.edu/u?/p245801coll10,34336.

Council of Science Editors:

Goldsmith ZG. Oncogenic Signaling Pathways Activated by Lysophosphatidic Acid (LPA) in Ovarian Carcinoma. [Doctoral Dissertation]. Temple University; 2009. Available from: http://digital.library.temple.edu/u?/p245801coll10,34336

Temple University

10. Gardner, Jacob Andrew. GPCR Signaling in the Genesis and Progression of Pancreatic Cancer.

Degree: PhD, 2009, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,35453

►

Molecular Biology and Genetics

Ductal adenocarcinomas of the pancreas are the 4th most common cause of cancer death. The 1 and 5 year survival rates… (more)

▼

Molecular Biology and Genetics

Ductal adenocarcinomas of the pancreas are the 4th most common cause of cancer death. The 1 and 5 year survival rates for all stages combined are currently 26% and 5% respectively. Median survival is less than 6 months. Despite remarkable progress in the fields of genetics, cancer biology, and advances in surgical techniques as well as chemotherapeutics, our ability to recognize and treat patients with pancreatic cancer remains poor. GPCR signaling modules have been increasingly implicated in the genesis and progression of pancreatic cancers. Aberrant agonist production, receptor expression and dysfunctional signaling resulting from genomic instability in a background of a heterotopic tumor-stromal microenvironment, contribute to the initiation, progression, and eventual metastasis of the disease. Numerous GPCR agonists, including lysophosphatidic acid (LPA), along with their cognate receptors have been implicated in this oncogenic process. LPA, one of the simplest bioactive lipids, has been shown to be a potent stimulant of metastatic behavior in in vitro models. It also acts as a mitogen by inducing proliferation and cell survival pathways in various normal and transformed cell lines. In patients with pancreatic cancer both the receptors and ligand have been found to be overexpressed. It has been noted that pancreatic cancer cell lines expressing higher levels of the LPA receptors present with greater motility. This has led to the hypothesis that LPA contributes to the progression of pancreatic cancer through the promotion of a metastatic phenotype. However, the underlying mechanisms have not been well described. LPA receptors have been shown to couple to the Gi, Gq, or G12 family of heterotrimeric G proteins. Consequently, signals transduced through these receptors have been shown to stimulate Gαi, Gαq, and Gα12/13 dependent pathways. While earlier studies have linked Gαi to LPA induced migration, there is recent evidence to suggest that Gα13 may provide a major signaling mechanism for LPA receptors stimulating migration in diverse cell types including cancer cell lines. Given the ominous nature of pancreatic cancers it is of critical importance to understand the mechanisms that promote more malignant phenotypes and to assess the role of Gα13 in this process. The goal of this thesis therefore is to define the role of Gα13 in LPA-mediated migration of pancreatic cancer cells. To assess the oncogenic potential of LPA and the role of Gα13 in stimulating the migration of pancreatic cancer cells, a panel of pancreatic cancer cell lines was assembled and characterized with regard to their expression of the LPA receptors as well as the Gα subunits of the heterotrimeric G proteins. These cell lines were further studied through a series of proliferation, wound healing, and transwell migration assays to assess the role of LPA in the induction of proliferation and migration in pancreatic cancer cells. The results demonstrated that LPA functions as a mitogen in certain pancreatic cancer…

Advisors/Committee Members: Dhanasekaran, Danny, Shore, Scott K., Athwal, Raghbir S., Haines, Dale, Ashby, Barrie.

Subjects/Keywords: Biology, Molecular; G alpha 13; GPCR; LPA; lysophosphatidic acid; Migration; Pancreatic Cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gardner, J. A. (2009). GPCR Signaling in the Genesis and Progression of Pancreatic Cancer. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,35453

Chicago Manual of Style (16^th Edition):

Gardner, Jacob Andrew. “GPCR Signaling in the Genesis and Progression of Pancreatic Cancer.” 2009. Doctoral Dissertation, Temple University. Accessed February 28, 2021. http://digital.library.temple.edu/u?/p245801coll10,35453.

MLA Handbook (7^th Edition):

Gardner, Jacob Andrew. “GPCR Signaling in the Genesis and Progression of Pancreatic Cancer.” 2009. Web. 28 Feb 2021.

Vancouver:

Gardner JA. GPCR Signaling in the Genesis and Progression of Pancreatic Cancer. [Internet] [Doctoral dissertation]. Temple University; 2009. [cited 2021 Feb 28]. Available from: http://digital.library.temple.edu/u?/p245801coll10,35453.

Council of Science Editors:

Gardner JA. GPCR Signaling in the Genesis and Progression of Pancreatic Cancer. [Doctoral Dissertation]. Temple University; 2009. Available from: http://digital.library.temple.edu/u?/p245801coll10,35453

University of California – San Diego

11. Lummis, Nicole Christine. Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss.

Degree: Biomedical Sciences, 2018, University of California – San Diego

URL: http://www.escholarship.org/uc/item/9q1782nq

► Lysophosphatidic acid (LPA) is a signaling phospholipid that binds to G protein-coupled receptors designated LPA1-LPA6. It has several activities throughout the body, including modulating cellular… (more)

Subjects/Keywords: Biology; Pharmaceutical sciences; cilia; ependymal cells; intracranial pressure; lysophosphatidic acid receptors; neonatal; post-hemorrhagic hydrocephalus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lummis, N. C. (2018). Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/9q1782nq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lummis, Nicole Christine. “Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss.” 2018. Thesis, University of California – San Diego. Accessed February 28, 2021. http://www.escholarship.org/uc/item/9q1782nq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lummis, Nicole Christine. “Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss.” 2018. Web. 28 Feb 2021.

Vancouver:

Lummis NC. Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Feb 28]. Available from: http://www.escholarship.org/uc/item/9q1782nq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lummis NC. Lysophosphatidic acid receptor 1 signaling initiates neonatal post-hemorrhagic hydrocephalus through ciliated ependymal cell loss. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/9q1782nq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

12. Mukherjee, Abir. ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM.

Degree: PhD, Biochemistry, 2012, Virginia Commonwealth University

URL: https://doi.org/10.25772/MH2Q-BQ19 ; https://scholarscompass.vcu.edu/etd/391

► The simplest phospholipid, lysophosphatidic acid (LPA), is a heat stable component of serum known for its proliferative and migratory activities in cancer cells. Strong… (more)

▼ The simplest phospholipid, lysophosphatidic acid (LPA), is a heat stable component of serum known for its proliferative and migratory activities in cancer cells. Strong evidence suggests that LPA production and expression of its receptors are dysregulated in multiple human malignancies. The mechanism behind LPA-mediated tumor cell growth and oncogenesis remains poorly understood. In this thesis project I used ovarian and other cancer cells as a model system to examine the hypothesis that LPA present in the tumor microenvironment is a pathophysiological determinant of hyperactive de novo lipogenesis and aerobic glycolysis, two hallmarks of cancer cells. We demonstrated that LPA induced proteolytic activation of sterol regulatory element binding proteins (SREBPs) in a cancer specific manner, leading to activation of the SREBP-FAS (fatty acid synthase) lipogenic pathway. Treatment of cancer cell lines with LPA also led to dephosphorylation and inhibition of AMP-activated kinase (AMPK), thereby activating acetyl CoA carboxylase (ACC). Moreover, these effects of LPA were mediated by LPA2, a receptor subtype overexpressed in multiple cancers, providing an explanation for the cancer specific regulation of FAS and ACC by LPA. Downstream of the LPA2 receptor, we identified the Gα12-Rho-Rock pathway to activate SREBPs and the Gαq-PLC (phospholipase C) pathway to inactivate AMPK. Consistent with LPA mediated activation of the key lipogenic enzymes FAS and ACC, LPA stimulated de novo lipid synthesis via LPA2, leading to accumulation of intracellular triacylglycerol and phospholipids. Pharmacological and molecular inhibition of LPA2, FAS or ACC attenuated LPA-dependent cell proliferation, indicating that upregulation of lipid synthesis is an integral component of the proliferative response to LPA. In further support of this, downregulation of LPA2 expression led to dramatic inhibition of anchorage-dependent and –independent growth of ovarian cancer cells. To support increased biomass generation, rapidly proliferating cancer cells enhance carbon influx by activating glycolysis. In the next part of the study, we investigated if LPA signaling was also involved in activating aerobic glycolysis in cancer cells. LPA indeed activated glycolysis in ovarian and other cancer cells but failed to elicit this response in non-transformed cells, suggesting a cancer specific role of LPA in regulation of glucose metabolism. While LPA had no effect on glucose uptake, we found that LPA altered expression of multiple genes involved in glucose metabolism. The most significant observation was that LPA treatment dramatically upregulated expression of HK-2, one of the rate-limiting glycolytic enzymes. We explored the underlying mechanism and found that LPA activates HK-2 transcription through LPA2-mediated activation of SREBP-1. Two sterol regulator elements (SREs) on the human HK-2 promoter were identified to be responsible for LPA activation of the promoter. DNA pulldown and chromatin immunoprecipitation assays confirmed that SREBP-1 bound to these… Advisors/Committee Members: Xianjun Fang.

Subjects/Keywords: Lysophosphatidic acid; Ovarian Cancer; GPCR; Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mukherjee, A. (2012). ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/MH2Q-BQ19 ; https://scholarscompass.vcu.edu/etd/391

Chicago Manual of Style (16^th Edition):

Mukherjee, Abir. “ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM.” 2012. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 28, 2021. https://doi.org/10.25772/MH2Q-BQ19 ; https://scholarscompass.vcu.edu/etd/391.

MLA Handbook (7^th Edition):

Mukherjee, Abir. “ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM.” 2012. Web. 28 Feb 2021.

Vancouver:

Mukherjee A. ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2012. [cited 2021 Feb 28]. Available from: https://doi.org/10.25772/MH2Q-BQ19 ; https://scholarscompass.vcu.edu/etd/391.

Council of Science Editors:

Mukherjee A. ROLE OF LYSOPHOSPHATIDIC ACID IN REGULATION OF CANCER CELL METABOLISM. [Doctoral Dissertation]. Virginia Commonwealth University; 2012. Available from: https://doi.org/10.25772/MH2Q-BQ19 ; https://scholarscompass.vcu.edu/etd/391

Virginia Commonwealth University

13. Mayton, Eric. Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method.

Degree: MS, Biochemistry, 2011, Virginia Commonwealth University

URL: https://doi.org/10.25772/2D7H-MH88 ; https://scholarscompass.vcu.edu/etd/2515

► Lysophosphatidic acid (LPA) is a bioactive lipid with a plethora of biological functions, including roles in cell survival, proliferation, and migration. Although high-performance liquid chromatography… (more)

Subjects/Keywords: Lysophosphatidic Acid; HPLC ESI-MS/MS; Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mayton, E. (2011). Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/2D7H-MH88 ; https://scholarscompass.vcu.edu/etd/2515

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mayton, Eric. “Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method.” 2011. Thesis, Virginia Commonwealth University. Accessed February 28, 2021. https://doi.org/10.25772/2D7H-MH88 ; https://scholarscompass.vcu.edu/etd/2515.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mayton, Eric. “Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method.” 2011. Web. 28 Feb 2021.

Vancouver:

Mayton E. Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method. [Internet] [Thesis]. Virginia Commonwealth University; 2011. [cited 2021 Feb 28]. Available from: https://doi.org/10.25772/2D7H-MH88 ; https://scholarscompass.vcu.edu/etd/2515.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mayton E. Characterization of Lysophosphatidic Acid Subspecies Using a Novel HPLC ESI-MS/MS Method. [Thesis]. Virginia Commonwealth University; 2011. Available from: https://doi.org/10.25772/2D7H-MH88 ; https://scholarscompass.vcu.edu/etd/2515

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

14. Battefeld, Arne. Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study.

Degree: 2012, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-5024

► The bioactive phospholipid lysophosphatidic acid (LPA) has an impact on cell- proliferation, apoptosis, cell-migration and development in the central nervous system, often via increases in… (more)

▼ The bioactive phospholipid lysophosphatidic acid (LPA) has an impact on cell- proliferation, apoptosis, cell-migration and development in the central nervous system, often via increases in intracellular calcium [Ca2+]i levels. The majority of the described LPA actions are g-protein mediated and both, receptors and signaling pathways are present in the brain. Thus, LPA mediated actions in the brain came into focus. In this thesis the patch-clamp technique was utilized to investigate neuromodulatory actions of LPA in mouse neurons. During brain development LPA actions are described. A family of LPA degrading enzymes the lipidphosphate phosphatases (LPPs) are present early in development. Reduced levels of LPP1/1a via shRNA in the embryonic brain resulted in a slowed migration of neocortical neurons. Neurons with changed LPP1/1a levels were electrophysiological profiled, because the maturation of ionic currents is tightly coupled to the migration of neurons. Neurons reaching their target at embryonic day 18 independent of their LPP1/1a levels did not differ. However, neurons that migrated slower due to shRNA expression did not generate regenerative potentials. A probable underlying cause was the same ratio of inward and outward rectifying conductances in contrast to a higher inward ratio in controls. On postnatal day 5 these neurons were mostly in layer 5 and no longer electrophysiologically different. In conclusion, the migration deficit lead to a delayed current development and an electrophysiological re-organisation of affected neurons in the neocortex. CA1 hippocampal neurons in accute brain slices responded to LPA. When LPA was applied extracellularly miniature excitatory postsynaptic currents (mEPSCs) increased in frequency. However, the inhibtory miniature postsynaptic currents (mIPSCs) were unchanged. The mEPSC increase was mediated by LPA2-receptors as there was no increase in LPA2-receptor knock-out mice. Further investigations were carried out in primary cultured hippocampal neurons to pin-point the LPA localisation. Contrary to accute slices the in vitro model responded with a reduction of mEPSCs. Neither mIPSCs of wildtype nor mEPSCs of LPA2 knock-out neurons were changed. The most probable modulation by calcium was further investigated. Buffering postsynaptic [Ca2+]i and applying LPA reduced mEPSCs whereas no reduction was observed after omitting extracellular Ca2+. These contrary results between accute slices and cultured neurons point to an involvement of glial factors and/ or artifacts as a result of culturing. Furthermore, the hyperpolarisation activated cyclic nucleotide gated current Ih can be modulated by g-protein signaling cascades. Activation of these, therefore, could lead to Ih modulation. A putative modulation was investigated in CA1 neurons, but somatic whole-cell recordings revealed no change of Ih. These results show that LPA-receptor activation is either not specific or a modification of Ih cannot be measured. Taken together these data show that lysophosphatidic acid has transient… Advisors/Committee Members: m (gender), PD Dr. Ulf Strauß (firstReferee), Prof. Dr. Hans-Joachim Pflüger (furtherReferee).

Subjects/Keywords: neurobiology; patch clamp; lysophosphatidic acid; neuronal action;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Battefeld, A. (2012). Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-5024

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Battefeld, Arne. “Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study.” 2012. Thesis, Freie Universität Berlin. Accessed February 28, 2021. http://dx.doi.org/10.17169/refubium-5024.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Battefeld, Arne. “Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study.” 2012. Web. 28 Feb 2021.

Vancouver:

Battefeld A. Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study. [Internet] [Thesis]. Freie Universität Berlin; 2012. [cited 2021 Feb 28]. Available from: http://dx.doi.org/10.17169/refubium-5024.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Battefeld A. Neuromodulatory actions of lysophosphatidic acid in vitro – a mouse study. [Thesis]. Freie Universität Berlin; 2012. Available from: http://dx.doi.org/10.17169/refubium-5024

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Tennessee – Knoxville

15. Rowland, Meng Meng. Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes.

Degree: 2011, University of Tennessee – Knoxville

URL: https://trace.tennessee.edu/utk_graddiss/1019

► Signaling lipids such as diacylglycerol (DAG) and the phosphatidylinositol polyphosphates (PIPns) play crucial roles in numerous cellular pathways. However, characterization of their activities is hindered… (more)

Subjects/Keywords: phosphoinositides; proteomics; click chemistry; photocrosslinking; lysophosphatidic acid; Biochemistry; Lipids; Medicinal and Pharmaceutical Chemistry; Organic Chemicals

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rowland, M. M. (2011). Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes. (Doctoral Dissertation). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_graddiss/1019

Chicago Manual of Style (16^th Edition):

Rowland, Meng Meng. “Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes.” 2011. Doctoral Dissertation, University of Tennessee – Knoxville. Accessed February 28, 2021. https://trace.tennessee.edu/utk_graddiss/1019.

MLA Handbook (7^th Edition):

Rowland, Meng Meng. “Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes.” 2011. Web. 28 Feb 2021.

Vancouver:

Rowland MM. Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes. [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2011. [cited 2021 Feb 28]. Available from: https://trace.tennessee.edu/utk_graddiss/1019.

Council of Science Editors:

Rowland MM. Chemical Tools to Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes. [Doctoral Dissertation]. University of Tennessee – Knoxville; 2011. Available from: https://trace.tennessee.edu/utk_graddiss/1019

University of Georgia

16. Nguyen, Ha Thu. The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer.

Degree: 2016, University of Georgia

URL: http://hdl.handle.net/10724/35434"

► Lysophasphatidic acid (LPA) is a mitogenic phospholipid present within the ovarian tumor microenvironment that induces ovarian cancer progression through multiple intracellular signaling cascades, leading to… (more)

▼ Lysophasphatidic acid (LPA) is a mitogenic phospholipid present within the ovarian tumor microenvironment that induces ovarian cancer progression through multiple intracellular signaling cascades, leading to cell growth, motility and proliferation. MicroRNAs (miRNAs) are small, non-protein-coding entities with important roles in post-transcriptional regulation of most of the human genome. Previously, we found that the expression of miR-30c-2-3p is induced by LPA and has an important role in the regulation of cell proliferation in ovarian cancer cells. The goals of this study were to examine the correlation between LPA and miR-30c-2-3p expression as well as mechanisms of miR-30c-2-3p antitumor effects. We observed that Dicer and epigenetic modifications, particularly DNA methylation and histone methylation, were not the major regulators of miR-30c-2-3p overexpression. Applying a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression of the transcription factor, ATF3. LPA triggers the expression of both miR-30c-2-3p and ATF3 in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3´-untranslated region (3´-UTR) of ATF3 was a predicted, putative target for miR-30c-2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter assay. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3 mRNA and protein after LPA stimulation. Thus, the data suggest that after the expression of ATF3 and miR-30c-2-3p are elicited by LPA, subsequently miR-30c-2-3p negatively regulates the expression of ATF3 through post-transcriptional silencing, which prevents further ATF3-related outcomes as a consequence of LPA signaling. Our in vivo pilot study shows evidence that miR-30c-2-3p can be a potential therapy for ovarian cancer. To date, there is limited information on miRNA mechanisms associated with LPA. Thus our findings bring in more understanding about the signaling circuits initiated by LPA, especially at the level of post-transcriptional silencing regulated by miRNAs. Furthermore, we provide experimental data to support the regulation of ATF3, another gene transcript targeted via miR-30c-2-3p, extending the current list, which includes BCL-9, HIF2A, X-box binding protein 1, Cyclin E1 and an adaptor protein of the NF-κB signaling pathway.

Subjects/Keywords: Ovarian cancer; MicroRNAs; miR-30c-2-3p; Lysophosphatidic acid (LPA); Activating Transcription Factor 3 (ATF3)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nguyen, H. T. (2016). The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/35434"

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nguyen, Ha Thu. “The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer.” 2016. Thesis, University of Georgia. Accessed February 28, 2021. http://hdl.handle.net/10724/35434".

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nguyen, Ha Thu. “The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer.” 2016. Web. 28 Feb 2021.

Vancouver:

Nguyen HT. The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer. [Internet] [Thesis]. University of Georgia; 2016. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10724/35434".

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nguyen HT. The regulations of miR-30c-3-3p and its antitumor mechanism in ovarian cancer. [Thesis]. University of Georgia; 2016. Available from: http://hdl.handle.net/10724/35434"

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky

17. Fulkerson, Zachary Bennett. LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS.

Degree: 2011, University of Kentucky

URL: https://uknowledge.uky.edu/physiology_etds/1

► Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth… (more)

▼ Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth muscle cell function. LPA has therefore been proposed as a mediator of cardiovascular disease. The bulk of circulating LPA is produced from plasma lysophosphatidylcholine (LPC) by autotaxin (ATX), a secreted lysophospholipase D (lysoPLD). Early studies suggest that some of the production of circulating LPA is platelet-dependent. ATX possesses an N-terminal somatomedin B-like domain suggesting the hypothesis that ATX interacts with platelet integrins which may localize ATX to substrate in the membrane and/or alter the catalytic activity of ATX. Using static adhesion and soluble binding assays we found that ATX does indeed bind to platelets and cultured mammalian cells in an integrin-dependent manner which is blocked by integrin function-blocking peptides and antibodies. This binding increases both the activity of ATX and localization of its product, LPA, to the platelet/cell membrane. LPA is generally stimulatory to human platelets although platelets from a small population of donors are refractory to LPA stimulation. Likewise LPA is inhibitory to murine platelets. We previously found that LPA receptor pan-antagonists reduce agonist-induced platelet activation, and partial stimulation of LPA5 specifically increases platelet activation in humans. Since both LPA5 and LPA4 are present at significant levels in human platelets, we hypothesized that LPA4 is responsible for an inhibitory pathway and LPA5 is responsible for an inhibitory pathway. We used mice deficient in LPA4 to test this model. Isolated platelet function tests revealed no major difference between lpa4-/- mice compared with WT mice although lpa4-/- mice were more prone to FeCl3-induced thrombosis. Paradoxically, chimeric mice reconstituted with lpa4-/- deficient bone marrow derived cells were protected from thrombosis. These discrepancies may be explained by involvement of endothelial cells and the relative scarcity of LPA receptors in murine platelets compared with human platelets. Taken together, these results demonstrate two critical regulators of LPA signaling and open up new avenues to further our understanding of atherothrombosis.

Subjects/Keywords: lysophosphatidic acid; platelet; autotaxin; signaling; integrin; G protein-coupled receptor; Biochemistry; Medical Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fulkerson, Z. B. (2011). LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/physiology_etds/1

Chicago Manual of Style (16^th Edition):

Fulkerson, Zachary Bennett. “LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS.” 2011. Doctoral Dissertation, University of Kentucky. Accessed February 28, 2021. https://uknowledge.uky.edu/physiology_etds/1.

MLA Handbook (7^th Edition):

Fulkerson, Zachary Bennett. “LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS.” 2011. Web. 28 Feb 2021.

Vancouver:

Fulkerson ZB. LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS. [Internet] [Doctoral dissertation]. University of Kentucky; 2011. [cited 2021 Feb 28]. Available from: https://uknowledge.uky.edu/physiology_etds/1.

Council of Science Editors:

Fulkerson ZB. LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS. [Doctoral Dissertation]. University of Kentucky; 2011. Available from: https://uknowledge.uky.edu/physiology_etds/1

18. Gerokonstantis, Triantafyllos - Dimitrios. Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης.

Degree: 2019, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/46788

►

Autotaxin (ATX), a glycoprotein (~ 125 kDa) isolated as an autocrine motility factor from melanoma cells, belongs to a seven-membered family of ectonucleotide pyrophosphatase /… (more)

▼

Autotaxin (ATX), a glycoprotein (~ 125 kDa) isolated as an autocrine motility factor from melanoma cells, belongs to a seven-membered family of ectonucleotide pyrophosphatase / phosphodiesterase (ENPP), and exhibits lysophospholipase D activity. ATX is responsible for the hydrolysis of lysophosphatidylcholine (LPC) to produce the bioactive lipid lysophosphatidic acid (LPA), which is upregulated in a variety of pathological inflammatory conditions, including fibrosis, cancer, liver toxicity, thrombosis etc. Given its role in human disease, the ATX-LPA axis is an interesting target for therapy, and the development of novel potent ATX inhibitors is of great importance. In the present work a novel class of ATX inhibitors, optically active derivatives of 2-pyrrolidinone and pyrrolidine heterocycles were synthesized. Some of them exhibited interesting in vitro activity, namely the hydroxamic acid 7 (IC50 700 nM), while the boronic acid derivatives 4α (IC50 50 nM), 4β (IC50 120 nM), 4γ (IC50 180 nM) and 4 (IC50 35 nM) were found to be potent inhibitors of ATX.

Η αυτοταξίνη (ΑΤΧ), μια γλυκοπρωτεΐνη (~125 kDa) που απομονώθηκε ως αυτοκρινής παράγοντας κινητικότητας από κύτταρα μελανώματος, ανήκει σε μια επταμελή οικογένεια εξωνουκλεοτιδίων πυροφωσφατάσης / φωσφοδιεστεράσης (ΕΝΡΡ) και έχει δράση λυσοφωσφολιπάσης D. H ATX είναι υπεύθυνη για την υδρόλυση της λυσοφωσφατιδυλοχολίνης (LPC) και την παραγωγή του βιοδραστικού λιπιδίου λυσοφωσφατιδικού οξέος (LPA), το οποίο υπερεκφράζεται σε διάφορες παθολογικές καταστάσεις φλεγμονής, όπως ίνωση, καρκίνος, ηπατική τοξικότητα, θρόμβωση και άλλα. Εξ αιτίας αυτής της δράσης, ο άξονας ATX-LPA αποτελεί έναν ενδιαφέροντα θεραπευτικό στόχο και η ανάπτυξη νέων ισχυρών αναστολέων για την ΑΤΧ αποκτά μεγάλο ενδιαφέρον. Στην παρούσα εργασία συντέθηκαν νέες ενώσεις, οπτικώς ενεργά παράγωγα των ετεροκυκλικών δακτυλίων της 2-πυρρολιδινόνης και της πυρρολιδίνης. Μερικές από αυτές επέδειξαν ενδιαφέρουσα in vitro ανασταλτική δραστικότητα έναντι της ΑΤΧ, όπως το υδροξαμικό οξύ 7, ενώ ισχυροί αναστολείς αποδείχθηκαν τα παράγωγα του βορονικού οξέος 4α, 4β, 4γ και κυρίως η ένωση 4, όπως φαίνεται στον παρακάτω πίνακα.

Subjects/Keywords: Αυτοταξίνη; Αναστολείς; Λυσοφωσφατιδικό οξύ; 2-πυρρολιδινόνη; Πυρρολιδίνη; Autotaxin; Inhibitors; Lysophosphatidic acid; 2-pyrrolidinone; Pyrrolidine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gerokonstantis, T. -. D. (2019). Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/46788

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gerokonstantis, Triantafyllos - Dimitrios. “Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης.” 2019. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed February 28, 2021. http://hdl.handle.net/10442/hedi/46788.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gerokonstantis, Triantafyllos - Dimitrios. “Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης.” 2019. Web. 28 Feb 2021.

Vancouver:

Gerokonstantis T-D. Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10442/hedi/46788.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gerokonstantis T-D. Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. Available from: http://hdl.handle.net/10442/hedi/46788

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

19. Fyffe-Freil, Ria C. Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation.

Degree: PhD, Molecular Biology and Genetics, 2020, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/6480

► Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year,… (more)

Subjects/Keywords: liver; transplantation; sphingosine; lysophosphatidic acid; organ preservation; ABC294640; Cellular and Molecular Physiology; Critical Care; Surgery

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fyffe-Freil, R. C. (2020). Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/6480

Chicago Manual of Style (16^th Edition):

Fyffe-Freil, Ria C. “Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation.” 2020. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 28, 2021. https://scholarscompass.vcu.edu/etd/6480.

MLA Handbook (7^th Edition):

Fyffe-Freil, Ria C. “Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation.” 2020. Web. 28 Feb 2021.

Vancouver:

Fyffe-Freil RC. Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2020. [cited 2021 Feb 28]. Available from: https://scholarscompass.vcu.edu/etd/6480.

Council of Science Editors:

Fyffe-Freil RC. Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation. [Doctoral Dissertation]. Virginia Commonwealth University; 2020. Available from: https://scholarscompass.vcu.edu/etd/6480

Penn State University

20. Winter, Jeremiah Nathanael. The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11094

► The mammalian target of rapamycin (mTOR) protein kinase exists in two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTORC1 signaling… (more)

▼ The mammalian target of rapamycin (mTOR) protein kinase exists in two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTORC1 signaling pathway is involved in numerous cellular processes, including cell growth and protein synthesis, as well as various physiological and pathophysiological conditions, including muscle hypertrophy, inflammation, cancer, and diabetes. Upstream of mTORC1 the tuberous sclerosis complex (TSC), comprised of TSC1 and TSC2, functions to inhibit mTORC1 signaling. This inhibition can be relieved by hormonal and lipid inputs, which induce the phosphorylation of TSC2 resulting in the inhibition of the TSC1/2 complex. In fact, the activation of mTORC1 is tightly regulated by nutrients, hormones, and lipids, particularly the branched chain amino acid (AA) leucine, insulin, and phosphatidic acid (PA) respectively. While the insulin-mediated activation of mTORC1 is largely elucidated, the mechanism through which PA and AAs function is not currently understood. Additionally, although the individual effect of each agonist on mTORC1 signaling has been studied, further research is required to identify the relative contribution of each input. Therefore, the first aim of this work was to identify the mechanism through which PA functions to stimulate mTORC1 activity. The present studies demonstrate that PA functions through a receptor based mechanism that stimulates the extracellular signal-regulated kinase (ERK) cascade. The inhibition of ERK signaling blocked the PA-mediated stimulation of mTORC1 signaling, clearly demonstrating that the primary mechanism utilized by PA to stimulate mTORC1 is activation of the ERK cascade. Additionally, AAs and PA signal to mTORC1 through parallel pathways, as mTORC1 signaling increased additively in response to leucine and PA treatments. This is significant since the literature suggests that AAs signal to mTORC1 through the production of PA. The second aim examined mTORC1 signaling in response to the activation of two signaling cascades that are involved in muscle hypertrophy, the ERK and protein kinase B (PKB) pathways. It was demonstrated that ERK and PKB, also called Akt, increased mTORC1 signaling through parallel pathways. The inhibition of either pathway reduced mTORC1 signaling partially in response to lysophosphatidic acid (LPA) and insulin treatment, which activate ERK and Akt respectively. The inhibition of both pathways completely blocked mTORC1 signaling in response to either agonist. Further, in the absence of TSC2, neither ERK nor Akt regulated mTORC1 signaling. This suggests that a functional TSC1/2 complex is required for the ERK- and Akt-mediated regulation of mTORC1 signaling. Overall, the data presented herein demonstrate that the combination of multiple stimulatory inputs increase mTORC1 signaling in an additive fashion. This is due to both TSC1/2 dependent and independent mechanisms, as LPA and insulin signal to mTORC1 through the inactivation of TSC1/2 while it is known that the leucine-mediated… Advisors/Committee Members: Leonard Shelton Jefferson Jr., Dissertation Advisor/Co-Advisor, Leonard Shelton Jefferson Jr., Committee Chair/Co-Chair, Scot R Kimball, Committee Member, Ralph Lauren Keil, Committee Member, David Antonetti, Ph D, Committee Member.

Subjects/Keywords: lysophosphatidic acid; TSC; ERK; Akt; protein kinase B; leucine; phosphatidic acid; PLD; mTORC1; LPAAT; PLA; Rag proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Winter, J. N. (2011). The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Winter, Jeremiah Nathanael. “The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex .” 2011. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/11094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Winter, Jeremiah Nathanael. “The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex .” 2011. Web. 28 Feb 2021.

Vancouver:

Winter JN. The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/11094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Winter JN. The Regulation of mTORC1 Signaling Through Multiple Simultaneous Stimulatory Inputs To The TSC1/2 Complex . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Faria, Kevin George. Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes.

Degree: 2019, University of Hertfordshire

URL: http://hdl.handle.net/2299/21790

► The use of stem cell-based therapy in conjunction with existing medical interventions, to target complications caused by coronary artery disease (CAD) is not fully examined.… (more)

▼ The use of stem cell-based therapy in conjunction with existing medical interventions, to target complications caused by coronary artery disease (CAD) is not fully examined. In parallel, the role of lysophosphatidic acid (LPA); an important endogenous bioactive phospholipid, has shown cardioprotective characteristics at low physiological concentrations, providing a potential for future treatment plans. In addition, studies have indicated the promise of aspirin (ASA)/ salicylic acid (SA) or LPA to induce and promote cardiac differentiation of SCs in various models. Therefore, in this project, we investigated the effects of ASA/SA in the presence or absence of LPA to induce the differentiation of the murine P19 teratocarcinoma stem cell line into cardiomyocytes. Routine cell culture was undertaken using P19 stem cells cultured in complete α-minimal essential medium (α-MEM). In the first instance, the protocol was optimised to ensure that efficient and reproducible differentiation was achieved. Embryoid bodies (EB) were formed by seeding cells and left to aggregate over a period of 2 days in ultra-low attachment 96-well plates, to establish differentiation. P19 stem cells were pre-incubated for 1 hour with ASA and SA at varying concentrations (0.1mM, 0.3mM, 1mM and 3mM) and selective NFκB inhibitor (0.1nM CAY10470) were pre-incubated 1 hour prior to adding LPA (5µM). Control cells were cultured in complete α-MEM alone. 6-8 EBs were isolated and seeded into 12-well tissue culture plates and cultured for 6 days. Western blotting was used to confirm differentiation, examining for the expression of ventricular myosin light chain (MLC-1v), relative to β-actin. To determine the potential mechanism through which differentiation may be induced, changes in phosphorylation of activated NFκB and IκB were determined. Optimisation of the differentiation protocol revealed that 1 x 104 cells grown for 2 days, produced consistent EBs sizes which ranged between 350-450µm in diameter. These EBs efficiently differentiated into cardiomyocytes. Differentiation was consistently achieved using LPA (5µM) and at selected concentrations of ASA (0.3 -1mM, at day 3) and SA (1mM, at day 3). Maximal expression of MLC-1v in ASA/SA conditions was seen at 1mM. However, LPA induced differentiation was inhibited by both in combination treatment with ASA and SA, despite both inducing differentiation independently. Analysis of phosphorylated and native proteins associated with the NFκB complex was successfully detected. These initial studies indicated substantial expression of phospho NFκB in LPA, SA and ASA treated cells and increases were seen at the 6-9-hour time points. The expression of phospho IκB in LPA treated cells peaked at 10-15 mins, while ASA/SA treated cells showed phospho IκB peaking at a later time point (3 hours). In conclusion, the experiments conducted in this thesis have shown that both ASA/SA and LPA induced cardiomyocyte differentiation. However, when ASA or SA are used in combination with LPA, an antagonistic effect is seen,…

Subjects/Keywords: P19 stem cells; cardiomyocytes; lysophosphatidic acid; MAP Kinases; Salicylic acid; Aspirin; Cyclooxygenase 1; Nuclear factor kappa B; NSAIDs; Thromboxane A2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Faria, K. G. (2019). Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes. (Masters Thesis). University of Hertfordshire. Retrieved from http://hdl.handle.net/2299/21790

Chicago Manual of Style (16^th Edition):

Faria, Kevin George. “Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes.” 2019. Masters Thesis, University of Hertfordshire. Accessed February 28, 2021. http://hdl.handle.net/2299/21790.

MLA Handbook (7^th Edition):

Faria, Kevin George. “Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes.” 2019. Web. 28 Feb 2021.

Vancouver:

Faria KG. Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes. [Internet] [Masters thesis]. University of Hertfordshire; 2019. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2299/21790.

Council of Science Editors:

Faria KG. Effect of Aspirin and Salicylic Acid on LPA Induced Differentiation of P19 Stem Cells into Cardiomyocytes. [Masters Thesis]. University of Hertfordshire; 2019. Available from: http://hdl.handle.net/2299/21790

22. Wattelet, Valérie. Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway.

Degree: Docteur es, Biologie Végétale, 2019, Bordeaux

URL: http://www.theses.fr/2019BORD0333

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Chez les eucaryotes, les lipides membranaires sont essentiels à la compartimentation et la régulation des voies de sécrétion. Par leurs propriétés physiques, ils sont essentiels… (more)

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Chez les eucaryotes, les lipides membranaires sont essentiels à la compartimentation et la régulation des voies de sécrétion. Par leurs propriétés physiques, ils sont essentiels aux courbures membranaires et à la régulation de la morphodynamique des endomembranes, de la morphologie des organites et de la formation des vésicules de transport. Chez l’animal, les acide lysophosphatidique acyltransférases (LPAATs) sont impliquées dans la régulation du trafic endomembranaire, mais rien n’est connu sur leur rôle chez la plante. Chez Arabidopsis thaliana, cinq LPAATs ont été identifiées. Nous avons déterminé leur activité enzymatique spécifique pour l'acide lysophosphatidique (LPA) pour produire de l'acide phosphatidique (PA). J'ai ensuite caractérisé leur localisation subcellulaire dans le système endomembranaire de la voie sécrétoire et étudié leur rôle présumé dans cette voie par approche génétique (mutants knock-out), biochimiques (inhibiteurs d'activité, analyses des lipides) et d'imagerie (microscopie confocale). En exploitant les lignées simples, doubles et triples mutantes des gènes LPAAT que j’ai produites, couplées à un traitement au CI-976 qui inhibe l'activité des LPAATs, j’ai montré suite à une analyse lipidique, que la quantité d’acide phosphatidique (PA) dépendante de l’activité LPAAT est essentielle pour l’adressage du transporteur d’auxine PIN2 et de l’aquaporine PIP2,7 vers la membrane plasmique.Ce travail souligne l’importance de la régulation des quantités de lipides dans les endomembranes et l’existence de seuils en-dessous desquels l’homéostasie membranaire peut être finement perturbée au point d’entraîner des disfonctionnements de la voie sécrétoire.

In eukaryotic cells, membrane lipids are essential for compartmentalization and regulation of secretory pathways. According to their physical properties, they are essential to membrane curvature and regulation of endomembrane morphodynamics, organelle morphology, and vesicles. In animal cells, lysophosphatidic acid acyltransferases (LPAAT) are involved in the regulation of endomembrane trafficking, but nothing is known about their role in plants. In Arabidopsis thaliana, five LPAATs were identified. We determined their specific enzymatic activity for lysophosphatidic acid (LPA) to produce phosphatidic acid (PA). I then characterized their subcellular localization in the endomembrane system of the secretory pathway and their potential role in this pathway using genetical (knockout mutants), biochemical (activity inhibitors, lipid analyzes) and imaging (confocal microscopy) approaches. Using the single, double and triple mutant lines for LPAAT genes that I produced, in addition to CI-976 treatment that inhibits LPAAT activity, I showed, after lipid analysis, that phosphatidic (PA) dependent on LPAAT activity is essential for the trafficking of the auxin carrier PIN2 and the aquaporin PIP2,7 to the plasma membrane.This work highlights the importance of lipid regulation in endomembranes and thresholds under which membrane homeostasis can be finely…

Advisors/Committee Members: Moreau, Patrick (thesis director).

Subjects/Keywords: Arabidopsis thaliana; Acide lysophosphatidique acyltransférase; Voie sécrétoire; Acide phosphatidique; Arabidopsis thaliana; Lysophosphatidic acid; Secretory pathway; Phosphatidic acid

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wattelet, V. (2019). Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2019BORD0333

Chicago Manual of Style (16^th Edition):

Wattelet, Valérie. “Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway.” 2019. Doctoral Dissertation, Bordeaux. Accessed February 28, 2021. http://www.theses.fr/2019BORD0333.

MLA Handbook (7^th Edition):

Wattelet, Valérie. “Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway.” 2019. Web. 28 Feb 2021.

Vancouver:

Wattelet V. Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway. [Internet] [Doctoral dissertation]. Bordeaux; 2019. [cited 2021 Feb 28]. Available from: http://www.theses.fr/2019BORD0333.

Council of Science Editors:

Wattelet V. Rôle des acide lysophosphatidique acyltransférases dans la voie sécrétoire chez les plantes : Role of lysophosphatidic acid acyltransferases in the plant secretory pathway. [Doctoral Dissertation]. Bordeaux; 2019. Available from: http://www.theses.fr/2019BORD0333

23. 山本, 淳平. ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ.

Degree: 博士（薬学）, 2017, Tokushima University / 徳島大学

URL: http://repo.lib.tokushima-u.ac.jp/110057

Subjects/Keywords: Lysophosphatidic acid; autotaxin/lysophospholipase D; oocyte maturation; implantation; pregnancy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

山本, �. (2017). ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ. (Thesis). Tokushima University / 徳島大学. Retrieved from http://repo.lib.tokushima-u.ac.jp/110057

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

山本, 淳平. “ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ.” 2017. Thesis, Tokushima University / 徳島大学. Accessed February 28, 2021. http://repo.lib.tokushima-u.ac.jp/110057.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

山本, 淳平. “ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ.” 2017. Web. 28 Feb 2021.

Vancouver:

山本 �. ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ. [Internet] [Thesis]. Tokushima University / 徳島大学; 2017. [cited 2021 Feb 28]. Available from: http://repo.lib.tokushima-u.ac.jp/110057.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

山本 �. ヒト卵胞液で産生されるリゾホスファチジン酸とその卵丘膨化促進作用 : ヒトランホウエキデサンセイサレルリゾホスファチジンサントソノランキュウボウカソクシンサヨウ. [Thesis]. Tokushima University / 徳島大学; 2017. Available from: http://repo.lib.tokushima-u.ac.jp/110057

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université de Sherbrooke

24. Harper, Kelly. Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4.

Degree: 2010, Université de Sherbrooke

URL: http://savoirs.usherbrooke.ca/handle/11143/4035

► Tumor metastasis is a fundamental property of malignant cancer cells and the major cause of death in cancer patients. Recent studies indicate that tumor cell… (more)

▼ Tumor metastasis is a fundamental property of malignant cancer cells and the major cause of death in cancer patients. Recent studies indicate that tumor cell invasion and metastasis may be initiated by the formation of the actin-rich cell protrusions with ECM degradation activity, invadopodia. However, despite extensive research on the biology of invadopodia, very little is known about their specific inducers during tumor progression. Autotaxin (ATX) is a secreted lysophospholipase whose expression levels within tumors correlates strongly with their aggressiveness and invasiveness. ATX produces lyosophosphatidic acid (LPA), a phospholipid with known tumor promoting functions that acts through the G-protein coupled receptors, LPA[subscript 1-6] . Recently, overexpression of ATX and LPA receptors (LPA[subscript 1-3]) has been linked to increased tumor invasion and metastasis in vivo , however, the role of other LPA receptors (LPA[subscript 4-6]) as well as the exact mechanisms by which ATX induces tumor metastasis remain poorly characterized. In order to determine the involvement of ATX and LPA in invadopodia production, we used the fibrosarcoma HT-1080 cells stably transfected with ATX or shRNA targeting ATX in fluorescent matrix degradation assays. Our results demonstrate that ATX is implicated in the production of invadopodia resulting in an increase in both their formation and function. Using LPC or LPA, the substrate and product of ATX, we further show that invadopodia production is dependent on the production of LPA from LPC. Among the LPA receptors, LPA 4 has the highest expression in HT1080 cells. Using LPA[subscript 4] shRNA as well as agonists and inhibitors of the cAMP pathway, we provide evidence that LPA[subscript 4] signaling through the cAMP-EPAC-Rap1 axis, regulates invadopodia formation downstream of ATX. Furthermore, inhibition of Rac1, a known effector of Rap1 and invadopodia formation, abolished EPAC-induced invadopodia production, suggesting downstream participation of Rac1. Finally, results using LPA[subscript 4] shRNA support the requirement of this receptor for in vitro cell invasion and in vivo metastasis formation. Our results suggest that ATX through LPA[subscript 4] is a strong inducer of invadopodia formation that correlates with the ability of the cells to invade and metastasize. This study also revealed an unexpected signaling pathway for cell invasion involving LPA[subscript 4]-driven cAMP production and subsequent activation of the EPAC-Rap1-Rac1 axis. Advisors/Committee Members: Dubois, Claire (advisor).

Subjects/Keywords: Metastasis; CAMP; Lysophosphatidic acid (LPA); Autotaxin; Invadopodia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harper, K. (2010). Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4. (Masters Thesis). Université de Sherbrooke. Retrieved from http://savoirs.usherbrooke.ca/handle/11143/4035

Chicago Manual of Style (16^th Edition):

Harper, Kelly. “Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4.” 2010. Masters Thesis, Université de Sherbrooke. Accessed February 28, 2021. http://savoirs.usherbrooke.ca/handle/11143/4035.

MLA Handbook (7^th Edition):

Harper, Kelly. “Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4.” 2010. Web. 28 Feb 2021.

Vancouver:

Harper K. Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4. [Internet] [Masters thesis]. Université de Sherbrooke; 2010. [cited 2021 Feb 28]. Available from: http://savoirs.usherbrooke.ca/handle/11143/4035.

Council of Science Editors:

Harper K. Autotaxin promotes cancer cell invasion via the lysophosphatidic acid receptor 4. [Masters Thesis]. Université de Sherbrooke; 2010. Available from: http://savoirs.usherbrooke.ca/handle/11143/4035

25. Maan, Gagandeep. Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells.

Degree: PhD, 2018, University of Hertfordshire

URL: http://hdl.handle.net/2299/21151

► The role of endogenous molecules in facilitating stem cell differentiation into cardiomyocytes is yet to be fully understood. SPC and S1P, common biolipids, promote cardiac… (more)

▼ The role of endogenous molecules in facilitating stem cell differentiation into cardiomyocytes is yet to be fully understood. SPC and S1P, common biolipids, promote cardiac differentiation of mesenchymal stem cells and cardiac progenitor cells, however, the same potential of closely related lysophosphatidic acid (LPA) has only recently become evident. The initial cardio-protection offered by elevated LPA levels in response to acute myocardial infarction and the ability of this biolipid to mediate other cellular fates served as a rationale to investigate the ability of LPA to mediate the cardiac differentiation of the murine P19 teratocarcinoma cell line and further examine the role of signalling molecules critical to lineage commitment. All experiments were carried out using P19 stem cells, cultured in supplemented alpha-minimal essential medium. Cells were aggregated into embryoid bodies in the presence of 5µM LPA in non-tissue grade Petri dishes over the course of 4 days to commence the differentiation process. Inhibitors were added 60 minutes before LPA while control cells were cultured in medium only. Embryoid bodies were transferred to 6-well tissue culture grade plates and cultured for a further 6 days. Cardiac differentiation was assessed by examining the expression of ventricular myosin light chain (MLC1v) by western blot and the role of LPA receptors 1-4, PKC, PI3K, MAPKs, and NF-κB were determined by examining the changes in this expression in the presence of selective inhibitors. The induction and regulation of GATA4, MEF2C, ATF-2, JNK, and YAP was also determined by western blotting. The activity and regulation of transcription factors, AP-1 and NF-κB, and the MAPKs was determined using ELISA kits. LPA induced the differentiation of P19 cells into cardiomyocytes most effectively when used at a concentration of 5µM as evidenced by the expression of MLC1v on day 10 of the differentiation process. Inhibition of LPA receptor 4 (0.1mg/mL Suramin), LPA receptors 1/3 (20µM Ki16425), LPA receptor 2 (7.5nM H2L5186303), PKC (10µM BIM-1), PI3K (20µM LY294002), ERK (20µM PD98059), JNK (10µM SP600125), and NF-κB (0.01nM CAY10470) blocked LPA induced expression of MLC1v. GATA4, MEF2C, pcJun, pJunD, and pATF2 expression increased in a time-dependent manner peaking at day 10 in LPA treated cells. GATA4 and pcJun expression was suppressed by all the inhibitors whereas MEF2C expression was unaffected by CAY10470, pJunD expression was unaffected by H2L5186303, pATF2 and NF-κB expression was unaffected by LY294002, but the latter was enhanced by Suramin. JNK was transiently phosphorylated in all cells whereas YAP was dephosphorylated 24-48 hours after EB formation in LPA treated cells and were both affected by Ki16425 and partially by H2L5186303 treatment. In conclusion, the studies carried out in this thesis have shown that LPA mediates the cardiac differentiation of P19 cells through LPA receptor 2, partially through receptors 1/3, and possibly through receptor 4. Conceivably downstream of these receptors, PKC, PI3K, MAPK,…

Subjects/Keywords: 616.1; Stem cells; Cardiomyocytes; P19 cells; Lysophosphatidic Acid; Cardiac Differentiation; LPA Receptors; MAP Kinases; Cardiac Transcription Factors

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maan, G. (2018). Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells. (Doctoral Dissertation). University of Hertfordshire. Retrieved from http://hdl.handle.net/2299/21151

Chicago Manual of Style (16^th Edition):

Maan, Gagandeep. “Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells.” 2018. Doctoral Dissertation, University of Hertfordshire. Accessed February 28, 2021. http://hdl.handle.net/2299/21151.

MLA Handbook (7^th Edition):

Maan, Gagandeep. “Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells.” 2018. Web. 28 Feb 2021.

Vancouver:

Maan G. Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells. [Internet] [Doctoral dissertation]. University of Hertfordshire; 2018. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2299/21151.

Council of Science Editors:

Maan G. Signal transduction mechanisms for lysophosphatidic acid mediated cardiac differentiation of P19 stem cells. [Doctoral Dissertation]. University of Hertfordshire; 2018. Available from: http://hdl.handle.net/2299/21151

University of Georgia

26. Ali, Mourad Wagdy Ahmed. Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/30280

► G-Protein coupled receptors (GPCRs) mediate a wide array of cellular functions, such as cell proliferation, migration, and survival. Regulators of G-protein signaling (RGS) proteins are… (more)

▼ G-Protein coupled receptors (GPCRs) mediate a wide array of cellular functions, such as cell proliferation, migration, and survival. Regulators of G-protein signaling (RGS) proteins are a diverse family of proteins that regulate signaling pathways downstream of GPCRs by acting on G-proteins. The focus of this dissertation is on the regulation of G-protein pathways in cancer and inflammation by RGS proteins, particularly by RGS10. We focused on signaling initiated by two related receptor families, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) receptors, which are implicated in ovarian cancer and neuroinflammation, respectively. Aberrant expression and mutations in RGS proteins have been implicated in diseases such as cancer and autoimmune disorders. The aim of this study was to define the function and the expression of RGS proteins, particularly RGS10, in ovarian cancer and microglia. LPA is the predominant growth factor in ovarian cancer, promoting proliferation, migration, and survival. RGS proteins negatively regulate LPA-mediated effects in ovarian cancer. We determined that RGS proteins, RGS10 and RGS17 regulate LPA-mediated survival in ovarian cancer cells. Specifically, our data demonstrate that RGS10 and RGS17 negatively regulate LPA-mediated AKT survival pathway in ovarian cancer cells. Further, we show that RGS10 and RGS17 are down-regulated in chemoresistant ovarian cancer cells, and our results show that RGS10 is epigenetically silenced in chemoresistant ovarian cancer cells via increased DNA methylation and decreased histone acetylation of the RGS10 promoter by DNA methyltransferase 1 (DNMT1), and histone deacetylase 1 (HDAC1), respectively. In addition to its role in chemoresistant ovarian cancer cells, RGS10 has been shown to exert an anti-inflammatory effect in microglia, the brain’s innate immune cells, via blunting pro-inflammatory cytokines signaling, and RGS10 is suppressed in activated microglia. We investigated the mechanism by which RGS10 is down-regulated in activated microglia, as well as the mechanism by which RGS10 regulates signaling pathways in microglia. Our results indicate that RGS10 is epigenetically suppressed via decreased histone acetylation of its promoter in activated microglia. Our results also suggest that RGS10 negatively regulates protein kinase A (PKA) and glycogen synthase kinase-3 beta (GSK-3β) downstream of lipopolysaccharide (LPS) and S1P, which may account for its regulation of pro-inflammatory cytokine signaling in activated microglia.

Subjects/Keywords: G-protein coupled receptors; regulator of G-protein signaling proteins; lysophosphatidic acid; sphingosine-1-phosphate; epigenetics; ovarian cancer; microglia.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ali, M. W. A. (2014). Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/30280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ali, Mourad Wagdy Ahmed. “Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia.” 2014. Thesis, University of Georgia. Accessed February 28, 2021. http://hdl.handle.net/10724/30280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ali, Mourad Wagdy Ahmed. “Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia.” 2014. Web. 28 Feb 2021.

Vancouver:

Ali MWA. Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10724/30280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ali MWA. Expression and function of regulator of G-protein signaling 10 (RGS10) in ovarian cancer and microglia. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/30280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

27. Turner, Kathryn Lisa. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/25339

► Lysophosphatidic acid (LPA) is a signaling molecule that induces survival, metastasis, migration, and proliferation in ovarian cancer cells by binding to G-protein coupled receptors (GPCRs),… (more)

Subjects/Keywords: LPA; Lysophosphatidic acid; Ovarian cancer; SKOV-3 cells; RGS; Regulator of G-protein signaling; G-protein; cAMP; Migration; RGS2; RGS19

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Turner, K. L. (2014). Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/25339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Turner, Kathryn Lisa. “Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.” 2014. Thesis, University of Georgia. Accessed February 28, 2021. http://hdl.handle.net/10724/25339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Turner, Kathryn Lisa. “Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.” 2014. Web. 28 Feb 2021.

Vancouver:

Turner KL. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10724/25339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Turner KL. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/25339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Nasraddin, Adem. Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes.

Degree: PhD, 2019, University of Hertfordshire

URL: http://hdl.handle.net/2299/22177

► Lysophosphatidic acid (LPA) is known to exert a diverse range of effects in humans, specifically in the heart where it may cause apoptosis of cardiomyocytes… (more)

▼ Lysophosphatidic acid (LPA) is known to exert a diverse range of effects in humans, specifically in the heart where it may cause apoptosis of cardiomyocytes at pathological concentrations. However, at physiological concentrations LPA may regulate cell migration, proliferation and even differentiation. The ability to drive stem cells down the cardiac lineage has, however not yet investigated and the potential underlying molecular mechanisms that could mediate this effect also remains to be determined. Since LPA is reported to accumulate in acute myocardial infarction and may rescue cardiac myocytes, we have hypothesised it may also be able to generate cardiac myocytes from stem cells. This hypothesis is based on observations that the signalling through which it exerts its biological effects are similar to those which have reported regulating stem cells regulation to various lineages. The aim of this thesis, therefore, was to study, firstly, the effectiveness of LPA in deriving cardiomyocytes and then to establish the molecular mechanisms involved focusing specifically on the expression profile of select miRNAs including mir-145, mir-1 and mir-133 which respectively linked to pluripotency and lineage commitments. All studies were carried out using the P19 stem cell line and were maintained and cultured in supplemented alpha-minimal essential medium (α-MEM), comprised of antibiotics and foetal bovine serum (FBS). Embryoid bodies were formed from aggregates of the cells in a non-tissue culture grade plates with or without LPA for four days. These EBs are subsequently plated in an adherent 6-well plate and maintained in culture between 3 and 12 days, before being lysed for either western blotting or RNA analysis. When used pharmacological inhibitors of LPA receptors (Suramin (P2 purinergic/LPA receptor 4), H2L5765834 (LPA receptor 1, 3 & 5), H2L5186303 (LPA receptor 2 & 3) and TC-LPA5-4 (LPA receptor 5)), targeted protein kinases (PKC; by BIM I) and PI3-kinase (by LY294002), they were added to the cultures 1 hour before treatment with LPA. In parallel studies, cells were transfected with mir-145 and mir-1 using siRNAs inhibitors or overexpression. The effect on MLC-1v and OCT4 protein expression then determined by western blotting. Successfully, the research revealed that LPA could achieve differentiation of P19 stem cells, and this was concentration and time-dependent. The maximum response was obtained with 20μM LPA and peaked on day 6. Subsequent experiments were carried out using 5 and/or 20μM LPA. Decreases paralleled the induction of MLC-1v in OCT4 expressions. The effects of LPA were mediated through its receptors, specifically LPA receptors 4 and 5 and partially on LPA receptors 2 and 3. The effects were also mediated through the kinases like protein kinase C, although the involvements of PI3 kinase was only partial. Expressions of mir-145, mir-1 and mir-133 elevated following treatment with LPA. Suramin, BIM-I inhibited these changes but not affected by LY294002, H2L5186303, H2L5765834 and TC-LPA5-4. Transfection…

Subjects/Keywords: Stem cells; miRNA; Development; Differentiation; Regulation; Post-transcription; Cardiovascular; Cardiomyocytes; LPA; Lysophosphatidic acid; P19 cell line

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nasraddin, A. (2019). Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes. (Doctoral Dissertation). University of Hertfordshire. Retrieved from http://hdl.handle.net/2299/22177

Chicago Manual of Style (16^th Edition):

Nasraddin, Adem. “Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes.” 2019. Doctoral Dissertation, University of Hertfordshire. Accessed February 28, 2021. http://hdl.handle.net/2299/22177.

MLA Handbook (7^th Edition):

Nasraddin, Adem. “Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes.” 2019. Web. 28 Feb 2021.

Vancouver:

Nasraddin A. Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes. [Internet] [Doctoral dissertation]. University of Hertfordshire; 2019. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2299/22177.

Council of Science Editors:

Nasraddin A. Role of microRNAs in LPA-induced regulation of stem cell differentiation into cardiomyocytes. [Doctoral Dissertation]. University of Hertfordshire; 2019. Available from: http://hdl.handle.net/2299/22177

Kyoto University

29. Toyotake, Yosuke. Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria .

Degree: 2019, Kyoto University

URL: http://hdl.handle.net/2433/242718

Subjects/Keywords: membrane lipid diversity; phospholipid biosythesis; lysophosphatidic acid acyltransferase; bacteria

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Toyotake, Y. (2019). Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/242718

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Toyotake, Yosuke. “Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria .” 2019. Thesis, Kyoto University. Accessed February 28, 2021. http://hdl.handle.net/2433/242718.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Toyotake, Yosuke. “Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria .” 2019. Web. 28 Feb 2021.

Vancouver:

Toyotake Y. Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria . [Internet] [Thesis]. Kyoto University; 2019. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2433/242718.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Toyotake Y. Studies of lysophosphatidic acid acyltransferases generating membrane lipid diversity in bacteria . [Thesis]. Kyoto University; 2019. Available from: http://hdl.handle.net/2433/242718

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Fotopoulou, Styliani. Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος.

Degree: 2011, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/27937

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Autotaxin (ATX), originally isolated from melanoma cells as a potent cell motility-stimulating factor, is a secreted lysophospholipase D that converts lysophosphatidyl choline (LPC) to lysophosphatidyl… (more)

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Autotaxin (ATX), originally isolated from melanoma cells as a potent cell motility-stimulating factor, is a secreted lysophospholipase D that converts lysophosphatidyl choline (LPC) to lysophosphatidyl Acid (LPA). LPA, an important lipid mediator, plays a crucial role in various neuronal developmental processes, including neurogenesis, neuronal migration, neuritogenesis and myelination. ATX mRNA expression is first detected at the floor plate of the neural tube at embryonic day 9.5 (E9.5), to reach widespread expression postnatally, with highest mRNA levels detected in brain, ovary and intestine. Enhanced ATX expression has been repeatedly demonstrated in a variety of malignant tumor tissues, including tumors of the central nervous system such as glioblastoma and neuroblastoma. To uncover the physiological role of ATX and LPA signalling in vivo we generated a conditionally inactivated allele by homologous recombination in embryonic stem cells (ES) using the Cre-LoxP system. To induce germ line, complete inactivation of ATX, ATXfl/fl mice were mated with transgenic mice overexpressing the Cre recombinase under the control of the human CMV minimal promoter. ATX-/- mice die at E9.5 with vascular defects in the yolk sac and severe malformations of the nervous system (open neural tube, asymmetric head folds, swollen alantois). We observe a dramatic increase in apoptosis accompanied by decrease in proliferation within the developing nervous system. Taken together, these results imply that ATX has antiapoptotic and a proliferative effect during neural development. The dorsal-ventral patterning is unaffected in Autotaxin null embryos. However neuronal differentiation is dramatically impaired but it can be rescued by LPA administration. Moreover, expression profiling using microarray data shows significant reduction of hypoxia inducible factor-1alpha (Hif1a). In the present study, we used mouse embryo fibroblasts to show that upon LPA stimulation there is expression of Hif1a. Previous studies suggest that in SCs, LPA exerts its survival effect through LPA receptor(s)-mediated Gi/o/PI3K/Akt survival pathways. Akt activity and Hif-1 are both essential for development and implicated in tumor growth. Upon activation by products of phosphatidylinositol 3-kinase (PI3K), Akt phosphorylates downstream targets that stimulate growth and inhibit apoptosis. We report here that, Akt was not expressed in ATX null embryos, indicating that Atx expression is necessary for the Hif-1 activation. These results indicate that ATX deficiency and LPA signaling plays a role in neuronal differentiation in the developing nervous system.

Η autotaxin (ATX) είναι μια εκκρινόμενη πρωτεΐνη με ενζυμική δράση λυσοφωσφολιπάσης D, η οποία μετατρέπει τη λυσοφωσφατιδυλχολίνη σε λυσοφωσφολιπιδικό οξύ (LPA). Η πλήρη απαλοιφή της ATX σε ποντίκια έχει ως αποτέλεσμα την ελαττωματική αγγειοπλασία, ανωμαλίες στο νευρικό σωλήνα που οδηγούν σε εμβρυικό θάνατο ηλικίας περίπου 10.5 ημερών. Στην παρούσα εργασία εστιάσαμε την μελέτη του ρόλου της ATX και της…

Subjects/Keywords: Λυσοφωσφατιδικό οξύ; Νευρωνική ανάπτυξη; Σκλήρυνση κατά πλάκας; Νόσος Alzheimer; Autotaxin; Lysophosphatidic acid; HIFI-A; Neuronal development; Multiple sclerosis; Alzheimer's disease

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fotopoulou, S. (2011). Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/27937

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fotopoulou, Styliani. “Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος.” 2011. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed February 28, 2021. http://hdl.handle.net/10442/hedi/27937.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fotopoulou, Styliani. “Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος.” 2011. Web. 28 Feb 2021.

Vancouver:

Fotopoulou S. Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2011. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/10442/hedi/27937.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fotopoulou S. Διερεύνηση του ρόλου της autotaxin και της μεταγωγής σήματος από φωσφολιπίδια στην ανάπτυξη και παθοφυσιολογία του νευρικού συστήματος. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2011. Available from: http://hdl.handle.net/10442/hedi/27937

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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